摘要
目的探讨丙戊酸钠（VPA）对不同性别APP／PSI双重转基因阿尔茨海默病（AD）模型小鼠的空间学习记忆能力及脑内老年斑（SP）的沉积的影响。方法3月龄APP／PS1双重转基因AD模型小鼠20只，雌雄各半，随机分为VPA治疗组和生理盐水对照组（每组10只）。VPA（30mg·kg^-1·d^-1）腹腔注射4周后进行Morris水迷宫实验，以检测各组小鼠的空间学习记忆能力；行为学实验结束后，取脑组织进行免疫组化染色以观察老年斑的沉积。结果行为学实验结果显示：可视平台下，两组小鼠找到平台的时间、搜索的平均路程以及雌雄小鼠的游泳速度均差异无显著性（P〉0．05）；隐蔽平台下，VPA治疗组小鼠找到平台的时间及搜索的平均路程较对照组明显缩短（P〈0．01），雄性AD模型鼠无论是治疗组还是对照组找到平台时间和路径均短于雌鼠（P〈0．05）；免疫组化结果显示，VPA治疗组雄性小鼠大脑皮质及海马区域的老年斑数量[（11．23±3．78）个]较同性别对照组[（28．17±3．46）个]明显减少（t=14．67，P〈0．01），且比雌性VPA治疗组老年斑[（20．36±4．21）个]也有明显减少（P〈0．05）。结论VPA能显著改善雌性和雄性AD模型小鼠空间学习记忆障碍，减少脑内老年斑的沉积，该改变具有性别差异。
Objective To investigate whether valproic acid （VPA） affect spatial learning memory and senile plaques in the APP/PS1 double transgenic AD mouse model of different gender. Methods Twenty 3-month old APP/PS1 double transgenic AD mice, male and female mouse evenly, were randomly divided into VPA-treated and saline-treated groups （10 for each group）. 30 mg·kg^-1·d^-1 of VPA and the same amount of saline were peritoneally injected into mice for 4 weeks. Morris water maze was conducted to check the effect of VPA on the capability of spatial learning and memory of AD mouse model. Immunohistoehemical staining was used to examine the effect of VPA on the morphological changes in the brains of mice. Results Visible platform test showed that VPA-treated and safine-treated mice had similar escape latency （P 〉 0.05） and path length （P〉 0.05） ,the swimming speed between male and female mice had no difference （P 〉 0.05 ）. Hidden platform test showed that VPA- treated mice had a significantly shorter latency （P〈0.01） and path length （P〈0.01） to reach the platform compared with saline-treated mice. Meanwhile, both in VPA-treated and control groups, the male mice had a shorter correlation escape latency and path-length than female mice had（P〈0.05 ）. Immuohistochemical staining showed that the number （11.23 ± 3.78） of senile plaques （SP） in the cerebral cortex and hippocampus of VPA-treated male mice were notably decreased than that（28.17 ± 3.46） in the control group （ t= 14.67, P〈0.01 ） ,further- more,the number of SP in the cerebral cortex and hippocampus of VPA-treated male mice was significantly reduced,as compared with which （20. 36 ±4.21）in the VPA-treated female mice（P〈0.05）. Conclusion VPA can significantly lower formation of SP, and remarkably improve the capability of spatial learning and memory of APP/PS1 transgenic mice ,which have gender difference.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2011年第3期205-207,共3页
Chinese Journal of Behavioral Medicine and Brain Science
基金
国家自然科学基金（30970986）
关键词
丙戊酸钠
阿尔茨海默病
性别
学习记忆
老年斑
Valproic acid
Alzheimer＇ s disease
Gender
Learning and memory
Senile plaques
